Stem cells have been identified in several somatic tissues including the nervous system, bone marrow, epidermis, skeletal muscle, and liver. This ‘set-aside’ population of cells is believed to be responsible for maintaining homeostasis within individual tissues in adult animals. The number of stem cells and their decision to differentiate must be tightly controlled during embryonic development and in the adult animal to avoid premature aging or tumor formation. Different somatic stem cells share the properties of self-renewal and multi-developmental potential, suggesting the presence of common cellular machinery.
Embryonic stem (ES) cells can proliferate indefinitely in an undifferentiated state. Furthermore, ES cells are pluripotent cells, meaning that they can generate all of the cells present in the body (bone, muscle, brain cells, etc.). ES cells have been isolated from the inner cell mass of the developing murine blastocyst (Evans et al., Nature 292:154-156, 1981; Martin et al., Proc. Natl. Acad. Sci. U.S.A. 78:7634-7636, 1981; Robertson et al., Nature 323:445-448, 1986; Doetschman et al., Nature 330:576-578, 1987; and Thomas et al., Cell 51:503-512, 1987; U.S. Pat. No. 5,670,372). Additionally, human cells with ES cell properties have recently been isolated from the inner blastocyst cell mass (Thomson et al., Science 282:1145-1147, 1998) and developing germ cells (Shamblott et al., Proc. Natl. Acad. Sci. U.S.A. 95:13726-13731, 1998) (see also U.S. Pat. No. 6,090,622, PCT Publication Nos. WO 00/70021 and WO 00/27995).
There is growing interest in the analysis of patterns of gene expression in cells, such as stem cells. However, few studies have identified an individual gene product that functions in the complex network of signals in developing tissues to inhibit differentiation and increase proliferation.